Photochemistry is becoming a powerful tool in the toolbox of organic and medicinal chemistry. Our overall goal is to further advance our photoassisted synthetic methodology which uses the recently discovered intramolecular cycloadditions of azaxylylenes photogenerated via excited state intramolecular proton transfer, ESIPT, as key photochemical steps to achieve the desired atom- and step economy, while delivering significant growth of molecular complexity in very few experimentally simple steps. As this photoassisted synthetic methodology matures, we focus our effort on synthesis of novel topologically diverse N,O,S-polyheterocycles, containing a large fraction of sp3 hybridized carbon atoms and stereogenic centers, and decorated by various functional groups and carbo/heterocyclic pendants rigidly or semi-rigidly held in a unique spatial configuration by these novel core frameworks with a minimal number of rotatable bonds. The specific aims of the proposed research are: (1) to develop rapid photoassisted access to complex polyheterocyclic molecular architectures containing ?-lactam moieties; (2) to develop rapid photoassisted access to 3D heterocycle-carbohydrate chimeras; (3) ?complexity-to- diversity:? to develop experimentally simple augmentation of complex natural products, e.g. aniline- or phenol-containing steroids or alkaloids, by linking them with photoactive cores, and photochemically modify them into diverse chimeric products including, as an example, unnatural enantiopure steroid alkaloids. Achieving a well-defined three-dimensional relationship within an assortment of functional groups and/or heterocyclic moieties is central to synthetic medicinal chemistry. The broad objective is to generate potential pharmacophores by systematically sampling the chemical space with diversified core structures augmented with a range of peripheral functionalities. With a few indications of biological activity in the preliminary studies, this project will involve targeted biological screening of compounds synthesized in the course of this study. As an AREA R15, this multifaceted project will provide ample training opportunities for graduate and undergraduate research students in the PI?s lab. The students will be involved with synthesis, learn photochemistry and photophysics, molecular modeling, spectra analysis and prediction, and gain initial understanding of medchem and biological screening.